Jonas Wenke, Schürmann Annette
Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, D-14558, Nuthetal, Germany; German Center for Diabetes Research (DZD), Ingolstädter Landstraße 1, D-85764, München-Neuherberg, Germany.
Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, D-14558, Nuthetal, Germany; German Center for Diabetes Research (DZD), Ingolstädter Landstraße 1, D-85764, München-Neuherberg, Germany; University of Potsdam, Institute of Nutritional Sciences, Arthur-Scheunert-Allee 114-116, D-14558, Nuthetal, Germany; Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology, Cottbus-Senftenberg, The Brandenburg Medical School Theodor Fontane and the University of Potsdam, Potsdam, Germany.
Mol Metab. 2021 Aug;50:101111. doi: 10.1016/j.molmet.2020.101111. Epub 2020 Nov 5.
Hepatic steatosis is a common chronic liver disease that can progress into more severe stages of NAFLD or promote the development of life-threatening secondary diseases for some of those affected. These include the liver itself (nonalcoholic steatohepatitis or NASH; fibrosis and cirrhosis, and hepatocellular carcinoma) or other organs such as the vessels and the heart (cardiovascular disease) or the islets of Langerhans (type 2 diabetes). In addition to elevated caloric intake and a sedentary lifestyle, genetic and epigenetic predisposition contribute to the development of NAFLD and the secondary diseases.
We present data from genome-wide association studies (GWAS) and functional studies in rodents which describe polymorphisms identified in genes relevant for the disease as well as changes caused by altered DNA methylation and gene regulation via specific miRNAs. The review also provides information on the current status of the use of genetic and epigenetic factors as risk markers.
With our overview we provide an insight into the genetic and epigenetic landscape of NAFLD and argue about the applicability of currently defined risk scores for risk stratification and conclude that further efforts are needed to make the scores more usable and meaningful.
肝脂肪变性是一种常见的慢性肝病，可进展为非酒精性脂肪性肝病（NAFLD）的更严重阶段，或促使部分患者发生危及生命的继发性疾病。这些疾病包括肝脏本身（非酒精性脂肪性肝炎或NASH；纤维化和肝硬化，以及肝细胞癌）或其他器官，如血管和心脏（心血管疾病）或胰岛（2型糖尿病）。除了热量摄入增加和久坐不动的生活方式外，遗传和表观遗传易感性也有助于NAFLD及其继发性疾病的发展。
我们展示了全基因组关联研究（GWAS）和啮齿动物功能研究的数据，这些研究描述了在与该疾病相关的基因中鉴定出的多态性，以及由特定miRNA引起的DNA甲基化改变和基因调控所导致的变化。该综述还提供了关于将遗传和表观遗传因素用作风险标志物的现状信息。
通过我们的综述，我们深入了解了NAFLD的遗传和表观遗传格局，并讨论了当前定义的风险评分在风险分层中的适用性，得出结论认为需要进一步努力使这些评分更具实用性和意义。
